Adults: Pre-treatment and on-treatment evaluations of anemia, iron stores and liver tests
Evaluation of anemia and iron stores
Correct and exclude other causes of anemia before starting Daprodustat (for example vitamin deficiency, metabolic or chronic inflammatory conditions, and bleeding). Evaluate the iron status of every patient before and during treatment with Daprodustat. Give supplemental iron when serum ferritin is less than 100 mcg/mL or when serum transferrin saturation is less than 20%. Most patients with CKD will need supplemental iron during the course of therapy.
Liver testing
Check serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and total bilirubin before starting Daprodustat. Repeat the liver tests if the patient develops signs or symptoms that could point to liver disease during treatment.
Important dosing information
Individualize the dosage and use the lowest dose of Daprodustat that is enough to reduce the need for red blood cell transfusions. Do not target a hemoglobin higher than 11 g/dL. Daprodustat can be taken with or without food, and it doesn't matter whether iron or phosphate binders are taken concomitantly. Swallow the tablets whole. They should not be cut, crushed or chewed. Daprodustat can be given regardless of the timing or type of dialysis. If a dose is missed, take it as soon as possible, unless it is the same day as the next dose. In that case, skip the missed dose and take the next one at the usual time. Don't take a double dose to make up for a missed one.
Recommended starting dose of Daprodustat
This applies to adults with anemia due to chronic kidney disease who have been receiving dialysis for at least 4 months.
Adults not being treated with an ESA
For adults not being treated with an ESA, the starting dose of Daprodustat depends on the hemoglobin level. The dosage needs modification for patients who are receiving concomitant treatment with a moderate CYP2C8 inhibitor, and for those with moderate hepatic impairment.
Monitoring response to therapy and dose adjustment
After starting therapy, and after each dose adjustment, monitor hemoglobin every 2 weeks for the first month and then every 4 weeks. When adjusting the dose of Daprodustat, consider how fast the hemoglobin is rising or falling, and how much it varies. Don't increase the dose more often than once every 4 weeks. Whether increasing or decreasing, move by one dose level at a time. Decrease the dose if hemoglobin rises rapidly (for example, more than 1 g/dL over 2 weeks or more than 2 g/dL over 4 weeks) or if hemoglobin goes above 11 g/dL. If hemoglobin goes above 12 g/dL, interrupt treatment with Daprodustat. Once hemoglobin is back within the target range, treatment may be restarted one dose level lower. Don't continue Daprodustat beyond 24 weeks if a clinically meaningful increase in hemoglobin level has not been achieved. Look for other explanations for the inadequate response, and treat them before restarting therapy.
Dosage modification for hepatic impairment
In patients with moderate hepatic impairment (Child-Pugh Class B), reduce the starting dose of Daprodustat by half, except where the starting dose is already 1 mg. Daprodustat is not recommended in patients with severe hepatic impairment (Child-Pugh Class C).
Dosage modification for concomitant treatment with moderate CYP2C8 inhibitors
In patients who are on clopidogrel or a moderate CYP2C8 inhibitor, reduce the starting dose of Daprodustat by half, except where the starting dose is already 1 mg. When clopidogrel or a moderate CYP2C8 inhibitor is started or stopped during treatment with Daprodustat, monitor hemoglobin and adjust the dose of Daprodustat.
